DONE BY :
BARAKATHU PEER FATHIMA
Phenylketonuria (PKU) is an autosomal
recessive metabolic genetic disorder characterized
by a mutation in the gene for the hepatic enzyme
phenylalanine hydroxylase (PAH), rendering it
nonfunctional. This enzyme is necessary to
metabolize the amino acid phenylalanine (Phe) to
the amino acid tyrosine. When PAH activity is
reduced, phenylalanine accumulates and is
converted into phenylpyruvate (also known as
phenylketone), which can be detected in the urine.
The enzyme phenylalanine
hydroxylase ( in the presence of
co-factor Tetrahydrobiopterin BH4)
normally converts the amino
acid phenylalanine into the amino
acid tyrosine. If this reaction does not
take place, phenylalanine accumulates
and tyrosine is deficient. Excessive
phenylalanine can be metabolized into
phenylketones through the minor
route, a transaminase pathway
with glutamate. Metabolites
include phenylacetate, phenylpyruvate
and phenethylamine. Elevated levels of
phenylalanine in the blood and
detection of phenylketones in the
urine is diagnostic, however most
patients are diagnosed via newborn
Phenylalanine is a large, neutral amino acid .
LNAAs compete for transport across the blood–
brain barrier via the large neutral amino acid
transporter . If phenylalanine is in excess in the
blood, it will saturate the transporter. Excessive
levels of phenylalanine tend to decrease the levels
of other LNAAs in the brain. However, as these
amino acids are necessary for protein and
neurotransmitter synthesis, Phe buildup hinders
the development of the brain, causing intellectual
A normal blood phenylalanine level is about
In cases of PKU, levels may range from 6-
80mg/dl, but are usually greater than
Chronically, high levels of phenylalanine and
some of its breakdown products can cause
significant brain problems.
There are other disorders of
hyperphenylalaninemia, but classic PKU is
the most common cause of high levels of
phenylalanine in the blood.
Phenylalanine accumulates, causing rashes,
seizures, hyperactivity, and mental
retardation, if untreated.
Prominent cheek and jaw bones widely
Poor development of tooth enamel.
It is important to remember that some
phenylalanine is needed to maintain
normal body function.
Insufficient phenylalanine intake may cause
mental and physical sluggishness, loss of
appetite, anemia, rashes, and diarrhea.
A single mutant recessive allele of the
Phenylalanine Hydroxylase (PAH) gene
Location : Long arm of Chromosome 12 -locus
PAH only allow a tolerance of 20 mg/kg/day.
Missense mutations and deletions.
Dietary excess of plant proteins which results in
the exhaustion of a protein cofactor
Tetrahydrobiopterin BH4 needed by the
Two people who conceive a child must
both be the carriers of the defective gene
in order for their child to have the
The “carrier” for PKU does not have the
It is recommended that women with
PKU who are of child bearing age, closely
adhere to the low-phenylalanine levels
before conception and throughout
pregnancy. The risk of miscarriage,
mental retardation, microcephaly, and
congenital heart disease in the child is
high if the mother’s blood phenylalanine
is poorly controlled.
The mean incidence of PKU varies
widely in different human
The PKU disorder is as frequent in
men as it is in women.
Country Incidence of PKU:
India 1 in 18,300
China 1 in 18,000
Finland 1 in 100,000
Ireland 1 in 4,500
Japan 1 in 120,000
Korea 1 in 41,000
Norway 1 in 13,000
Turkey 1 in 2,600
United States1 in 15,000
Usually a few drops of
blood are obtained by
a small prick on the
heel, placed on a card
and then sent for
All babies are screened for PKU by heel-
Blood tested for excess phenylalanine.
Blood placed on agar plate with bacteria
that need phenylalanine to grow.
Healthy babies’ blood doesn’t have extra
phenylalanine, so bacteria can’t grow.
Babies with PKU have extra
phenylalanine, so bacteria grow.
Bacterial plate with newborn blood
Negative controls: no
Positive blood test results:
bacterial halo = PKU
Negative blood test results:
no bacterial growth =
Positive controls : increasing
give bacterial halos
Ferric chloride + urine of new born
baby→ Green colour in the presence
of ketone bodies.
A strictly controlled phenylalanine free diet
up to the age of about 14 years old.
Phenylalanine is itself an essential amino acid
small doses must be supplied.
After 14 years, the growth and development of the
brain is not affected by high levels of
phenylalanine in the body.
Individuals with PKU must be alert for
food sweetened with aspartame - artificial
sweetener made from amino acids
phenylalanine and aspartic acid.
If PKU goes untreated or undetected,
severe brain problems occur such as
seizures and mental retardation.
More frequent doctor visits.
Required dietary restrictions that may
impact day to day activities.
Permanent monitoring of blood